A Study of MGC018 in Combination With MGD019 in Participants With Advanced Solid Tumors

A Phase 1/1b Dose Escalation and Cohort Expansion Study of MGC018 in Combination With Checkpoint Inhibitor in Participants With Advanced Solid Tumors

Study CP-MGC018-02 is a study of vobramitamab duocarmazine (MGC018) in combination with lorigerlimab. The study is designed to characterize safety, tolerability, pharmacokinetics (PK), immunogenicity, pharmacodynamics, and preliminary antitumor activity. Participants with relapsed or refractory, unresectable, locally advanced or metastatic solid tumors including, but not limited to, mCRPC, melanoma, pancreatic cancer, hepatocellular carcinoma (HCC), ovarian cancer, and renal cell carcinoma (RCC) will be enrolled. Vobramitamab duocarmazine and lorigerlimab are administered separately on Day 1 of every 4-week (28-day) cycle at the assigned dose for each cohort. Participants who do not meet criteria for study drug discontinuation may receive study drugs for up to 2 years. Tumor assessments are performed every 8 weeks for the initial 6 months on study drugs, then every 12 weeks (± 21 days) until progressive disease (PD). Participants will be followed for safety throughout the study. .

Advanced Solid Tumor, Castration-Resistant Prostatic Cancer, Malignant Melanoma, Pancreatic Ductal Carcinoma, Hepatocellular Cancer, Epithelial Ovarian Cancer, Renal Cell Carcinoma

Cycle 1 Day 1 Preinfusion, end of infusion (EOI [1-hour]), 2 hours and 5 hours after EOI, Day 8; Day 15; Cycle 2 Day 1 Preinfusion, EOI, 1 hour after EOI; Day 8; Day 15; Day 1 of subsequent cycles pre-infusion and EOI (every 4 weeks) up to 2 years

Cycle 1 Day 1 Preinfusion, end of infusion (EOI [1-hour]), 1 hour and 4 hours after EOI, Day 8, Day 15; Cycle 2 Day 1 Preinfusion, EOI, 1 hour after EOI; Day 8, Day 15; Day 1 of subsequent cycles pre-infusion and EOI (every 4 weeks) up to 2 years

Cycle 1 Day 1 Preinfusion, end of infusion (EOI [1-hour]), 2 hours and 5 hours after EOI, Day 8; Day 15; Cycle 2 Day 1 Preinfusion, EOI, 1 hour after EOI; Day 8, Day 15; Day 1 of subsequent cycles pre-infusion and EOI (every 4 weeks) up to 2 years.

Cycle 1 Day 1 Preinfusion, end of infusion (EOI [1-hour]), 1 hour and 4 hours after EOI, Day 8; Day 15; Cycle 2 Day 1 Preinfusion, EOI, 1 hour after EOI; Day 8, Day 15; Day 1 of subsequent cycles pre-infusion and EOI (every 4 weeks) up to 2 years.

Area under the concentration-time curve during the dosing interval (AUCtau) of vobramitamab duocarmazine

Concentration of vobramitamab duocarmazine in the bloodstream during the 28-day dosing interval after dose administration

Cycle 1 Day 1 Preinfusion, end of infusion (EOI [1-hour)], 2 hours and 5 hours after EOI, Day 8; Day 15; Cycle 2 Day 1 Preinfusion, EOI, 1 hour after EOI; Day 8, Day 15; Day 1 of subsequent cycles pre-infusion and EOI (every 4 weeks) up to 2 years.

Concentration of lorigerlimab in the bloodstream during the 28-day dosing interval after dose administration

Cycle 1 Day 1 Preinfusion, end of infusion (EOI [1-hour]), 1 hours and 4 hours after EOI, Day 8; Day 15; Cycle 2 Day 1 Preinfusion, EOI, Day 8, Day 15; Day 1 of subsequent cycles pre-infusion and EOI (every 4 weeks) up to 2 years.

PFS is defined as the time from the first dose date to the date of first documented PD or death from any cause, whichever occurs first.

Assessed every 8 weeks for the first 6 months, then every 12 weeks. Survival status is assessed approximately every 12 weeks after the last dose of study treatment until withdrawal of consent, lost to follow up, death, or end of the study, up to 2 years.

DoR is defined as the time from the date of initial response (CR or PR) to the date of first documented PD or death from any cause, whichever occurs first.

Survival status is assessed approximately every 12 weeks after the last dose of study treatment until withdrawal of consent, lost to follow up, death, or end of the study, up to 2 years

rPFS is defined as the time from the first dose of study drug to the first occurrence of radiographic PD of soft tissue lesions using RECIST v1.1, or appearance of ≥ 2 new bone lesions, or death from any cause

PSA response is defined as ≥ 50% decline from baseline in PSA with confirmation at least 3 weeks later.

PSA is assessed every 4 weeks, up to 2 years while on treatment, then every 12 weeks for up to an additional 2 years in follow-up.

PSA is assessed every 4 weeks, up to 2 years while on treatment, then every 12 weeks for up to an additional 2 years in follow-up.

PSA progression is defined as an increase that is ≥ 25% and ≥ 2 ng/mL the baseline or lowest value observed, and which confirmed by a second value at least 3 weeks later.

PSA is assessed every 4 weeks, up to 2 years while on treatment, then every 12 weeks for up to an additional 2 years in follow-up.

DoR of PSA is defined as the time from the date of initial PSA response to the date of first documented PSA progression or death from any cause, whichever occurs first.

PSA is assessed every 4 weeks, up to 2 years while on treatment, then every 12 weeks for up to an additional 2 years in follow-up.

Inclusion Criteria: 1. Ability to provide and document informed consent and willing and able to comply with all study procedures. Participants diagnosed with advanced solid tumors including but not limited to metastatic castration-resistant prostate cancer, melanoma, pancreatic cancer, hepatocellular carcinoma, ovarian cancer and renal cell carcinoma. Participants have received approved therapies according to their diagnosis. Participants must have an available tumor tissue sample. A fresh tumor biopsy may be performed if no archival sample is available. Eastern Cooperative Oncology Group performance status of less than or equal to 2. Life expectancy of at least 12 weeks. Evidence of measurable tumor for evaluation Acceptable end organ function according to laboratory results. Patients must agree to use highly-effective contraception during the study, and not donate sperm or ova. Exclusion Criteria: Any underlying medical or psychiatric condition impairing participant's ability to receive, tolerate, or comply with the planned treatment or study procedures. Another malignancy that required treatment within the past 2 years. Participants who have had curative therapy for non-melanomatous skin cancer, localized prostate cancer (Gleason score < 6), or carcinoma in situ are eligible for the study. Active viral, bacterial, or fungal infection requiring systemic treatment within 1 week of initiation of study drug. Participants are eligible after SARS CoV 2-related symptoms have fully recovered for ≥ 72 hours. History of immunodeficiency. Participants with HIV are eligible if they have a CD4+ count ≥ 300/µL, undetectable viral load, and maintained on antiretroviral therapy for a minimum of 4 weeks. Prior autologous/allogeneic stem cell or tissue/solid organ transplant Prior treatment with MGD009, enoblituzumab, or other B7-H3 targeted agents for cancer. Clinically significant cardiovascular disease, lung compromise, venous insufficiency, or gastrointestinal disorders. Participants with greater than Grade 1 peripheral neuropathy. Participants who have a history of severe adverse events (AEs) from immune checkpoint inhibitors (anti-PD-1, anti-PD-L1, or CTLA-4 inhibitors). All other AEs from prior immune checkpoint inhibitors must be resolved to Grade 1 or less. Participants with any grade neurologic toxicity from prior immune checkpoint inhibitors are excluded. Pleural effusion or ascites. Trace pleural or peritoneal fluid is not exclusionary. History of Guillain-Barre syndrome, myasthenia gravis, or other autoimmune sensory or motor neuropathies.